A metagenomic strategy for harnessing the chemical repertoire of the human microbiome

Abstract

Extensive progress has been made in determining the effects of the microbiome on human physiology and disease, but the underlying molecules and mechanisms governing these effects remain largely unexplored. Here, we combine a new computational algorithm with synthetic biology to access biologically active small molecules encoded directly in human microbiome–derived metagenomic sequencing data. We discover that members of a clinically used class of molecules are widely encoded in the human microbiome and that they exert potent antibacterial activities against neighboring microbes, implying a possible role in niche competition and host defense. Our approach paves the way toward a systematic unveiling of the chemical repertoire encoded by the human microbiome and provides a generalizable platform for discovering molecular mediators of microbiome-host and microbiome-microbiome interactions.

The need to innovate sample collection and library generation in microbial drug discovery: a focus on academia

“…[10][11][12][13] Compared to what is known, researchers have just begun to map the cues that govern the vast array of inter-and intra-species relationships in the environment, and recent studies that focus on the human microbiome highlight just one area of particular promise. 14,15 In regard to untargeted sample collections, three fundamental questions that can inform collection strategies are: (1) How are NP biosynthetic genes distributed in the environment? ; (2) How are NP biosynthetic genes distributed across taxa?…”

Masthead - Full issue pdf

“…Very recently, a team in Princeton took this approach to the next level [10]. Using diff erent computational tools, they analysed bacterial genomes and identifi ed gene clusters that codifi ed the biosynthesis of small molecules.…”

Secretion of and Self-Resistance to the Novel Fibupeptide Antimicrobial Lugdunin by Distinct ABC Transporters in Staphylococcus lugdunensis

“…The capacity to produce bacteriocins and related molecules has been found to be particularly abundant in microbiome members from nutrient-poor habitats such as the human nose (6). We are only beginning to understand the diversity and relevance of such molecules (7).…”